CA2334761C - Composition comprenant de l'acide .beta.-hydroxy-.beta.-methylbutyrique et au moins un amino-acide, et methodes d'utilisation correspondantes - Google Patents

Composition comprenant de l'acide .beta.-hydroxy-.beta.-methylbutyrique et au moins un amino-acide, et methodes d'utilisation correspondantes Download PDF

Info

Publication number
CA2334761C
CA2334761C CA002334761A CA2334761A CA2334761C CA 2334761 C CA2334761 C CA 2334761C CA 002334761 A CA002334761 A CA 002334761A CA 2334761 A CA2334761 A CA 2334761A CA 2334761 C CA2334761 C CA 2334761C
Authority
CA
Canada
Prior art keywords
hmb
composition
arginine
animal
glutamine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
CA002334761A
Other languages
English (en)
Other versions
CA2334761A1 (fr
Inventor
Steven L. Nissen
Naji M. Abumrad
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Iowa State University Research Foundation ISURF
Original Assignee
Iowa State University Research Foundation ISURF
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22292520&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CA2334761(C) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Iowa State University Research Foundation ISURF filed Critical Iowa State University Research Foundation ISURF
Publication of CA2334761A1 publication Critical patent/CA2334761A1/fr
Application granted granted Critical
Publication of CA2334761C publication Critical patent/CA2334761C/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Virology (AREA)
  • Diabetes (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Emergency Medicine (AREA)
  • Neurology (AREA)
  • Nutrition Science (AREA)
  • Molecular Biology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pulmonology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

L'invention concerne une composition comprenant de l'acide beta -hydroxy- beta -méthylbutyrique (HMB) et au moins un amino-acide. La présente invention concerne également une méthode de traitement de la fonte musculaire d'un animal liée à la maladie, une méthode permettant de réduire le taux sérique des triglycérides d'un animal, une méthode de réduction de la charge virale sérique d'un animal, une méthode de redistribution des graisses dans un animal ayant une zone viscérale et un zone sous-cutanée, une méthode permettant d'accroître la masse maigre d'un animal sans réduction sensible de sa masse adipeuse, et une méthode permettant d'accroître le niveau de cholestérol HDL chez un animal. Toutes ces méthodes impliquent l'administration d'une composition comprenant de l'acide beta -hydroxy- beta -méthylbutyrique et au moins un amino-acide à l'animal.
CA002334761A 1998-06-23 1999-06-23 Composition comprenant de l'acide .beta.-hydroxy-.beta.-methylbutyrique et au moins un amino-acide, et methodes d'utilisation correspondantes Expired - Lifetime CA2334761C (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/102,941 1998-06-23
US09/102,941 US6031000A (en) 1998-06-23 1998-06-23 Composition comprising β-hydroxy-β-methylbutyric acid and at least one amino acid and methods of use
PCT/US1999/014097 WO1999066917A2 (fr) 1998-06-23 1999-06-23 COMPOSITION COMPRENANT DE L'ACIDE β-HYDROXY-β-METHYLBUTYRIQUE ET AU MOINS UN AMINO-ACIDE, ET METHODES D'UTILISATION CORRESPONDANTES

Publications (2)

Publication Number Publication Date
CA2334761A1 CA2334761A1 (fr) 1999-12-29
CA2334761C true CA2334761C (fr) 2009-04-28

Family

ID=22292520

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002334761A Expired - Lifetime CA2334761C (fr) 1998-06-23 1999-06-23 Composition comprenant de l'acide .beta.-hydroxy-.beta.-methylbutyrique et au moins un amino-acide, et methodes d'utilisation correspondantes

Country Status (12)

Country Link
US (1) US6031000A (fr)
EP (1) EP1089726B1 (fr)
JP (2) JP5064609B2 (fr)
AU (1) AU756353B2 (fr)
CA (1) CA2334761C (fr)
DE (1) DE69901396T2 (fr)
DK (1) DK1089726T3 (fr)
ES (1) ES2177293T3 (fr)
NO (2) NO329914B1 (fr)
NZ (1) NZ508395A (fr)
PL (1) PL195623B1 (fr)
WO (1) WO1999066917A2 (fr)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3362350B2 (ja) * 1997-10-16 2003-01-07 味の素株式会社 反芻動物の肥育方法
US20040220266A1 (en) * 2002-09-09 2004-11-04 Wiley David B. Composition and method for enhancing the bioavailability of calcium and magnesium in dietary supplements and food additives
US20040106678A1 (en) * 2002-09-17 2004-06-03 Dobbins Thomas A Compositions for the parenteral administration of calcium and magnesium
US6812249B2 (en) * 2003-03-04 2004-11-02 Sal Abraham Process for preparing a 3-hydroxy-3-methylbutyrate amino acid salt and method of use
US20050215640A1 (en) 2004-03-26 2005-09-29 Baxter Jeffrey H HMB compositions and uses thereof
EP1973426A2 (fr) * 2005-11-03 2008-10-01 Southwest Immunology Inc. Compositions visant a prevenir et reduire les courbatures du lendemain
BRPI0619179A2 (pt) * 2005-11-30 2011-09-13 Nestec Sa métodos para o tratamento de perda muscular
NZ568611A (en) 2005-12-19 2011-11-25 Abbott Lab Use of beta-hydroxy-beta-methylbutyrate to modulate the imbalance in type 1 and type 2 cytokine production
US7754693B2 (en) * 2006-02-16 2010-07-13 Young Hee Ko Composition and method for the efficacious and safe administration of halopyruvate for the treatment of cancer
US8324175B2 (en) 2006-02-16 2012-12-04 Young Hee Ko Compositions and methods for the treatment of cancer
US11173167B2 (en) 2008-12-09 2021-11-16 Metabolic Technologies, Inc. Nutritional intervention for improving muscular function and strength
US9707241B2 (en) 2008-12-09 2017-07-18 Metabolic Technologies, Inc. Nutritional intervention for improving muscular function and strength
US9770424B2 (en) * 2008-12-09 2017-09-26 Metabolic Technologies, Inc. Nutritional intervention for improving muscular function and strength
US9539224B2 (en) * 2008-12-09 2017-01-10 Metabolic Technologies, Inc. Nutritional intervention for improving muscular function and strength
US9259430B2 (en) 2008-12-09 2016-02-16 Metabolic Technologies, Inc. Nutritional intervention for improving muscular function and strength
DK2381784T3 (en) 2008-12-09 2018-10-22 Metabolic Tech Inc Nutritional intervention to improve muscle function and strength
CA2750944C (fr) * 2009-01-29 2019-01-08 Young Hee Ko Compositions et procedes pour le traitement du cancer
EP2289555A1 (fr) * 2009-08-24 2011-03-02 OrgaNext Research B.V. Procédé de traitement des faiblesses
JP6077857B2 (ja) * 2009-12-18 2017-02-08 メタボリック・テクノロジーズ，インコーポレーテッド β−ヒドロキシ−β−メチル酪酸塩（ＨＭＢ）の改善された投与方法
US9693577B2 (en) 2010-01-29 2017-07-04 Abbott Laboratories Method of preparing a nutritional powder comprising spray dried HMB
AU2011210682A1 (en) 2010-01-29 2012-07-05 Abbott Laboratories Aseptically packaged nutritional liquids comprising HMB
AU2011210691A1 (en) 2010-01-29 2012-07-12 Abbott Laboratories Nutritional emulsions comprising calcium HMB
TWI526161B (zh) 2010-06-10 2016-03-21 亞培公司 包含鈣ｈｍｂ及可溶性蛋白質之實質上透明營養液
JP6158801B2 (ja) 2011-07-15 2017-07-05 ニューサート サイエンシーズ， インコーポレイテッド 代謝経路を変調させるための組成物および方法
WO2013067485A1 (fr) 2011-11-03 2013-05-10 University Of Florida Research Foundation, Inc. Supplément nutritionnel pour la gestion du poids
US20130143968A1 (en) * 2011-11-21 2013-06-06 Emmaus Medical, Inc. Methods and compositions for the treatment of diabetes and related symtoms
WO2013106570A1 (fr) 2012-01-11 2013-07-18 Abbott Laboratories Combinaison de bêta-hydroxy-bêta-méthylbutryate, d'arginine et de glutamine utilisée dans le traitement des ulcères diabétiques
US9198454B2 (en) 2012-03-08 2015-12-01 Nusirt Sciences, Inc. Compositions, methods, and kits for regulating energy metabolism
PL3733171T3 (pl) 2012-09-10 2024-03-18 Metabolic Technologies, LLC Kompozycje zawierające hmb i atp oraz ich zastosowanie
JP6346896B2 (ja) 2012-09-21 2018-06-20 アボット・ラボラトリーズＡｂｂｏｔｔ Ｌａｂｏｒａｔｏｒｉｅｓ カルシウムβ−ヒドロキシ−β−メチルブチレート、タンパク質および低レベルの電解質を含む栄養組成物
WO2014047493A1 (fr) * 2012-09-21 2014-03-27 Abbott Laboratories Compositions nutritionnelles comprenant le bêta-hydroxy-bêta-méthylbutyrate de calcium et une protéine
SG10201709195TA (en) 2012-11-13 2017-12-28 Nusirt Sciences Inc Compositions and methods for increasing energy metabolism
MX2015012821A (es) * 2013-03-14 2016-05-31 Abbott Lab Tratamiento de resistencia a la insulina asociado con la inactividad fisica prolongada.
CA2902879C (fr) 2013-03-15 2023-09-26 Nusirt Sciences, Inc. Leucine et acide nicotinique reduisant les taux de lipides
US20150057350A1 (en) * 2013-08-23 2015-02-26 Abbott Laboratories Fibrosis biomarkers and methods of using same
CN106456997B (zh) 2014-02-27 2018-12-28 纽斯尔特科学公司 用于减少或预防肝性脂肪变性的组合物和方法
EP3302704B1 (fr) * 2015-06-01 2023-01-25 Metabolic Technologies, Inc. Compositions et procédés d'utilisation de bêta-hydroxy-bêta-méthylbutyrate (hmb) pour la diminution de la masse graisseuse
WO2017049093A1 (fr) 2015-09-16 2017-03-23 Metabolic Technologies, Inc. Compositions et procédés d'utilisation de butyrate de ss-hydroxy-ss-méthyle (hmb) pour améliorer la récupération après un traumatisme d'un tissu mou
JP6875288B2 (ja) * 2015-11-19 2021-05-19 協和発酵バイオ株式会社 ３−ヒドロキシイソ吉草酸の一価カチオン塩の結晶および該結晶の製造方法
BR122023026038A2 (pt) 2016-01-21 2024-01-16 Metabolic Technologies, Inc. Usos de um ácido e de um modulador de autofagia e de lipofagia
US11026929B2 (en) 2016-04-19 2021-06-08 Keto Patent Group, Inc. Administration of berberine metabolites
WO2017184788A1 (fr) * 2016-04-19 2017-10-26 Keto Patent Group, Inc. Administration de butyrate, de bêta-hydroxybutyrate et de composés apparentés à des humains
CN109476578A (zh) 2016-06-24 2019-03-15 协和发酵生化株式会社 3-羟基异戊酸氨基酸盐的晶体及其制造方法
CN110167544A (zh) 2016-10-21 2019-08-23 代谢科技有限公司 β-羟基-β-甲基丁酸(HMB)和益生菌的组合物及使用方法
JOP20190146A1 (ar) * 2016-12-19 2019-06-18 Axcella Health Inc تركيبات حمض أميني وطرق لمعالجة أمراض الكبد
CN111295187A (zh) 2017-08-14 2020-06-16 胺细拉健康公司 用于治疗肝脏疾病的氨基酸组合物
KR20200131810A (ko) * 2018-01-05 2020-11-24 텍사스 테크 유니버시티 오피스 오브 리서치 커머셜라이제이션 간헐적 금식과 관련된 β-하이드록시-β-메틸부티레이트 (HMB)의 조성물 및 사용 방법
EP3810123A1 (fr) 2018-06-20 2021-04-28 Axcella Health Inc. Compositions et procédés pour le traitement de l'infiltration de graisse dans le muscle

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5157022A (en) * 1989-11-22 1992-10-20 Adrian Barbul Method for reducing blood cholesterol using arginine
US5028440A (en) * 1990-01-30 1991-07-02 Iowa State University Research Foundation, Inc. Method of raising meat producing animals to increase lean tissue development
US4992470A (en) * 1990-02-08 1991-02-12 Iowa State University Research Foundation, Inc. Method of enhancing immune response of mammals
ES2142353T3 (es) * 1992-09-16 2000-04-16 Univ Iowa State Res Found Inc Procedimiento para reducir los niveles de colesterol total y de colesterol asociado a lipoproteinas de baja densidad en sangre.
US5348979A (en) * 1992-12-23 1994-09-20 Iowa State University Research Foundation Inc. Method of promoting nitrogen retention in humans
AU6102994A (en) * 1993-02-11 1994-08-29 Iowa State University Research Foundation Inc. Method of enhancing nutritional value of colostrum and first milk of pregnant mammals
US5726146A (en) * 1994-12-06 1998-03-10 Natural Supplement Association, Incorporated Non-steroidal, anabolic dietary supplement and method to increase lean mass without linked increase fat mass
US5756469A (en) * 1996-07-26 1998-05-26 Beale; Paxton K. Composition of pyruvate and anti-cortisol compounds and method for increasing protein concentration in a mammal
DE29707308U1 (de) * 1997-04-23 1997-06-26 Kunz, Armin, 66450 Bexbach Präparat zur Muskelerhaltung bzw. zur Förderung des Muskelaufbaus

Also Published As

Publication number Publication date
WO1999066917A3 (fr) 2000-04-20
WO1999066917A2 (fr) 1999-12-29
JP2012102118A (ja) 2012-05-31
NZ508395A (en) 2003-09-26
EP1089726A2 (fr) 2001-04-11
NO329914B1 (no) 2011-01-24
PL195623B1 (pl) 2007-10-31
JP5064609B2 (ja) 2012-10-31
PL344589A1 (en) 2001-11-05
NO20101440L (no) 2001-02-20
AU756353B2 (en) 2003-01-09
US6031000A (en) 2000-02-29
ES2177293T3 (es) 2002-12-01
NO332374B1 (no) 2012-09-10
JP2002518440A (ja) 2002-06-25
EP1089726B1 (fr) 2002-05-02
NO20006633L (no) 2001-02-20
JP5690261B2 (ja) 2015-03-25
DE69901396D1 (de) 2002-06-06
DK1089726T3 (da) 2002-07-22
DE69901396T2 (de) 2002-08-29
NO20006633D0 (no) 2000-12-22
AU4708099A (en) 2000-01-10
CA2334761A1 (fr) 1999-12-29

Similar Documents

Publication Publication Date Title
CA2334761C (fr) Composition comprenant de l'acide .beta.-hydroxy-.beta.-methylbutyrique et au moins un amino-acide, et methodes d'utilisation correspondantes
EP2512236B1 (fr) Procédé amélioré permettant d'administrer du bêta-hydroxy-bêta-méthylbutyrate (hmb)
AU664511B2 (en) Method of promoting nitrogen retention in humans
US5453282A (en) Dietary lipid digestion-absorption inhibitory agents and ingesta
RU2195934C2 (ru) Высокие дозы трипиколината хрома для лечения диабета второго типа
JP2008534599A (ja) 高齢者の骨格筋量減少を防止又は改善するためのアミノ酸含有組成物
US5431925A (en) Nutritive composition for prevention and therapy of infection diseases caused by immunosuppression
KR20050089857A (ko) 간암 발생 및 진행 억제제
EP0786993B1 (fr) Compositions comprenant de l'acide dichloroacetique tamponne au carbonate/bicarbonate et leur utilisation dans le traitement de troubles metaboliques et cardiovasculaires
JP3622985B2 (ja) マグネシウム吸収を高め、アテローム性動脈硬化症を防ぐ方法
JP3908513B2 (ja) 肝機能改善剤
KR100304312B1 (ko) 아연이보충된전립선추출물
EP4331583A1 (fr) Agent augmentant la carnitine sanguine
MXPA00011686A (es) Composicion que comprende acido beta-hidroxi-beta-metilbutirico y al menos un aminoacido y metodos de uso
CN114177185B (zh) 一种用于降低胆固醇与预防心血管疾病的药物组合物
CA3218375A1 (fr) Composition pour augmenter la masse musculaire
WO1996011679A1 (fr) Compositions comprenant de l'acide dichloroacetique tamponne au carbonate/bicarbonate et procedes de traitement de troubles metaboliques et cardiovasculaires
JP2001316272A (ja) 高尿酸血症又は痛風の予防又は改善剤

Legal Events

Date Code Title Description
FZDC Discontinued application reinstated
EEER Examination request
MKEX Expiry

Effective date: 20190625